Mice Deficient in Mac-1 (CD11b/CD18) Are Less Susceptible to Cerebral Ischemia/Reperfusion Injury

Abstract

Background and Purpose-Macrophage-1 antigen (Mac-1) (CD11b/CD18), a leukocyte ␤2 integrin, facilitates neutrophil adhesion, transendothelial migration, phagocytosis, and respiratory burst, all of which may mediate reperfusion-induced injury to ischemic brain tissue in conditions such as stroke. To determine the role of Mac-1 during ischemia and reperfusion in the brain, we analyzed the effect of transient focal cerebral ischemia in mice genetically engineered with a specific deficiency in Mac-1. Methods-Transient focal ischemia/reperfusion was induced by occluding the left middle cerebral artery for 3 hours followed by a 21-hour reperfusion period in Mac-1-deficient (nϭ12) and wild-type (nϭ11) mice. Regional cerebral blood flow was determined with a laser-Doppler flowmeter. Brain sections were stained with 2% 2,3,5-triphenyltetrazolium chloride to determine the infarct volume. Neutrophil accumulation was determined by staining the brain sections with dichloroacetate esterase to identify neutrophils. Results-Compared with the wild-type cohort, Mac-1-deficient mice had a 26% reduction in infarction volume (PϽ0.05).This was associated with a 50%, but statistically insignificant, reduction in the number of extravasated neutrophils in the infarcted areas of the brains in the mutant mice. There were no differences in regional cerebral blood flow between the 2 groups. Conclusions-Mac-1 deficiency reduces neutrophil infiltration and cerebral cell death after transient focal cerebral ischemia. This finding may be related to a reduction in neutrophil extravasation in Mac-1-deficient mice. (Stroke. 1999;30:134-139.)

Microglial Activation in Stroke: Therapeutic Targets

“…92 Expression of the fractalkine receptor, CX3CR1, is observed only on microglia and macrophages, suggesting that fractalkine is involved in neuron-microglial signaling. 91 Mice deficient in fractalkine 93 or its microglial receptor 94 have smaller infarct sizes and better functional outcomes. CX3CR1 antagonists are currently under development.…”

Lymphocyte Function-Associated Antigen-1-Dependent Inhibition of Corneal Wound Healing

“…19 -22 The contributions of each integrin have been investigated with blocking antibodies, specific inhibitors, or in mice with targeted deletions of either integrin. In acute models of neutrophildependent tissue injury, removal or blocking of Mac-1 has been effective in reducing tissue damage, 14,[23][24][25][26][27] whereas in more complex models involving other leukocytes and adaptive immune processes, removal or blocking LFA-1 has been effective in reducing tissue pathology. 14,28 -30 In addition to the varying contributions of these two integrins in models with different pathological etiologies, differences in vascular beds appear as well.…”

cis-Ampelopsin E, a Stilbene Isolated from the Seeds of Paeonia suffruticosa, Inhibits Lipopolysaccharide-Stimulated Nitric Oxide Production in RAW 264.7 Macrophages via Blockade of Nuclear Factor-Kappa B Signaling Pathway

“…Stimulation of inflammatory cells activates PLA 2 to hydrolyze glycerophospholipids and release arachidonic acid (AA). 30,31) AA is next metabolized through the cyclooxygenase (Cox) 32) or lipoxygenase (Lox) pathways [33][34][35] to prostaglandin H 2 (PGH 2 ), the precursor of the series-2 prostanoids. There are two isoforms of cyclooxygenase, namely Cox-1 and Cox-2.…”